Premium
Characterization of unmyelinated axons uniting epidermal and dermal immune cells in primate and murine skin
Author(s) -
Egan Christine L.,
ViglioneSchneck Mary J.,
Walsh Laurence J.,
Green Barry,
Trojanowski John Q.,
WhitakerMenezes Diana,
Murphy George F.
Publication year - 1998
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/j.1600-0560.1998.tb01685.x
Subject(s) - pathology , human skin , dermis , substance p , mast cell , cutaneous nerve , immune system , biology , epidermis (zoology) , cytokine , microbiology and biotechnology , anatomy , neuropeptide , immunology , medicine , receptor , biochemistry , genetics
The present study was undertaken to characterize further the structure and function of cutaneous nerves which we have previously shown to associate with skin immune cells (Hosoi et al., Nature 1993: 363:159). Ultrastructurally, axons were prominent within the superficial dermis atid epidermis in neonatal murine skin, but they were inconspicuous in adult murine and primate skin. Immunohistochemical and immunoultrastuctural evaluation of normal adult human and simian skin for neural cell adhesion molecule (N‐CAM), however, defined a plexus of axons surrounding superficial dermal mast cells and extending as delicate, vertical branches into the overlying epidermal layer. Antibodies to neuropeptides substance P, calcitonin gene‐related peptide, and to nerve cell‐specific clathrin (LCb subunit) also reacted with this neural plexus. Double labeling disclosed intimate associations of N‐CAM‐positive axons with dermal chymase‐positive mast cells as well as with epidermal CD la‐positive Langerhans' cells by confocal scanning laser microscopy. Functionally, capsaicin applied to forearm skin revealed by 6 h discharge of mast cell chymase and induction of E‐selectin in adjacent microvascular endothelium, events consistent with release of substance P from axons and subsequent stimulation of cytokine‐mediated mast cell‐endothelial interaction. Identical application of capsaicin to human skin xenografted to immunodeficient mice, and thus experimentally lacking in unmyelinated axons, failed to show similar findings. These results provide additional support to the concept that an elaborate network of cutaneous axons may play a functional role in regulation of skin inflammation and immunity.